KR20150051075A - A body hair growth inhibition composition comprising palmatine as an effective ingredient - Google Patents

Abstract

The present invention relates to a composition containing palmatine (palmatine) as an active ingredient for inhibiting the growth of body hairs. The composition of the present invention suppresses the cell division or proliferation of follicle cells and inhibits the growth of hairs. The composition of the present invention has no toxicity and has no side effects if the composition is applied to a human body. The composition is useful in the removal or decrease of hairs in a local area.

Description

A hair growth inhibition composition comprising palmatin as an active ingredient,

The present invention relates to a composition for inhibiting hair growth comprising palmatin as an active ingredient. More specifically, the present invention relates to a cosmetic composition for inhibiting hair growth comprising palmatin as an active ingredient. The present invention also relates to a pharmaceutical composition for inhibiting hair growth comprising palmatin as an active ingredient.

Hair is a generic term for hairs and hair, which develops from the skin and develops as a skin appendage. The hair repeats the anagen, ctagen, and talogens and has a cycle of growth, elimination, and initiation.

Hair is essentially an organ that has been functioning to protect the body but is degenerating with evolution. Human beings are covered with fur all but palms, soles, lips, and hairs, and the number is between 120 and 1.5 million. The hair is divided into hardness and softness by hardness. The moxa is black and hard with hair, eyebrow hair, eyelash hair, etc. The soft hair is soft and soft hair. In recent years, not only the coarse hairs on the side such as the armpit and the leg but also the hair on the whole body such as the human hair for the purpose of beauty are increasing.

Existing hair removal methods are largely divided into physical hair removing method (eg razor) and chemical hair removing method (eg hair removing cream), waxing or tweezers to remove the hair from the root, Have been used. These methods have the disadvantage that they cause irritation to the skin when used over a long period of time, as well as roughness of the skin, contact dermatitis and pigmentation, and the use thereof is limited for wound areas and some parts such as the face.

Therefore, there is a demand for development of a hair growth inhibitor that can overcome these drawbacks and at the same time show less hair irritation and show hair removal effect by utilizing the hair growth cycle and the differentiation principle of hair follicle cells.

Under these circumstances, the inventors of the present invention confirmed that palmatin inhibits cell differentiation and proliferation of hair follicle cells to inhibit the growth of hair, and further confirmed that it has excellent hair removal effect when applied to human body, thereby completing the present invention Respectively.

The present invention aims at inhibiting hair growth by using a composition containing palmatin as an active ingredient.

Specifically, the present invention provides a composition for inhibiting hair growth, which has an effect of inhibiting the growth and proliferation of hair follicle cells by containing palmatin as an active ingredient.

In order to solve the above-described problems, the present invention provides a cosmetic composition for inhibiting hair growth comprising palmatine as an effective ingredient.

According to another embodiment of the present invention, there is provided a pharmaceutical composition for inhibiting hair growth comprising palmatin as an active ingredient.

In another embodiment of the present invention, the palmain is represented by the following general formula (1).

[Chemical Formula 1]

In another embodiment of the present invention, the palmatin is characterized by inhibiting the differentiation or proliferation of hair follicle cells.

In another embodiment of the present invention, the palmatin is characterized by inhibiting the expression of ornithine decarboxylase (ODC) gene.

In another embodiment of the present invention, the content of palmain may be 0.0005% to 5% by weight of the total composition.

In another embodiment of the present invention, the composition may have a formulation selected from the group consisting of liquid, oil, cream, ointment, stick, pack, pasta, powder, gel and spray, It does not.

Hereinafter, the present invention will be described in detail.

The present invention is based on the fact that palmatin has the effect of inhibiting the differentiation and proliferation of hair follicle cells.

The term "palmatine" used in the present invention is preferably a compound represented by the following formula (1), and the compound is 2,3,9,10-tetramethoxy-5,6-dihydroisoquinoline Lt; / RTI > [2,1-b] isoquinolin-7-yl.

[Chemical Formula 1]

Palmin is an organic compound derived from palmitic acid, which is needle-like yellow color. Palmatin has been reported to have therapeutic effects on hypertension, inflammation and liver-related diseases. However, there is no study on the inhibitory activity of hair growth.

The palmatin of the present invention exhibits an effect of inhibiting the differentiation or proliferation of hair follicle cells, and this effect was first identified in the present invention.

The hair follicle cell refers to a stem cell that produces hair existing in a hair follicle.

The term " differentiation of hair follicle cells " means a process in which hair follicles are formed by repeating cleavage and forming hard keratin.

The proliferation of the hair follicle cells means a process of increasing the number of cells by repeating the division of the hair follicle cells.

Specifically, in one embodiment of the present invention, it was confirmed that the hair follicle cell proliferation was inhibited when the composition containing the palmatin as an active ingredient was treated.

In addition, the palmatin of the present invention has an effect of inhibiting the expression of ornithine decarboxylase.

The present inventors have found that polyamine plays an important role in differentiation, division or proliferation of hair follicle cells, and that ornithine dicarboxylate is an enzyme necessary for biosynthesis of polyamines, and that the above-mentioned palmatin and ornithine diamine The relationship between the expression of the enzyme and the enzyme was studied.

Thus, in one embodiment of the present invention, when follicle dermal papilla cells were treated with palmatin at different concentrations, cell counts were compared using Cell Counting Kit-8, and palmatin inhibited the proliferation of follicular cells in a concentration-dependent manner (Example 1).

In another embodiment of the present invention, the cells expressing ornithine dicarboxylate are expressed at a concentration of palmatin, and the relative expression is compared using reverse transcription polymerase chain reaction (RT-PCR) As a result, it was confirmed that palmatin suppressed the expression of ornithine decarboxylase in a concentration-dependent manner (Example 3).

Inhibiting the expression of the enzyme preferably means reducing the expression of the enzyme at the transcription level.

In addition, it has been confirmed that, in one embodiment of the present invention, when palmatin is formulated into an external ointment or cream formulation and applied to human skin, it exhibits excellent hair growth inhibitory effect (Examples 4 and 5).

Therefore, the palmatin of the present invention has an effect of reducing the production and growth of new hair follicles, so that it can be effectively used as an effective ingredient of a hair growth inhibitor.

Accordingly, the present invention also provides a use of palmatin for the production of a cosmetic composition for inhibiting hair growth or a pharmaceutical composition for inhibiting hair growth, and a hair growth inhibition method comprising applying palmatin to the skin in an effective amount.

The palmatine of the present invention may contain palmatin hydrate, palmatin derivative, and the like within a range having the same effect, and may include a solvent or a stereoisomer thereof. The palmatine may be chemically synthesized or extracted directly from natural materials, or a commercially available palmate may be purchased and used. When the palmartin is separated from a natural substance, it may be a concept including all of natural substance extracts or fractions thereof, as long as it contains palmain.

The palmatine used in one embodiment of the present invention was purchased from XI'AN JIATIAN BIOTECHNOLOGY CO., LTD.

The term "hairs" used in the present invention refers collectively to hairs distributed in the body. The distribution of the hairs is not particularly limited. However, for the purpose of the present invention, it is preferable that the hairs are distributed in a body part which causes harm to aesthetics due to occurrence, growth, or excessive distribution of hairs such as armpits, arms, It can mean hair.

The term "hair growth inhibition" used in the present invention includes not only inhibiting hair growth or growth, slowing hair growth rate, but also reducing hair thickness or length.

The palmatin of the present invention can be preferably added to an external preparation for skin hair growth inhibition, but is not limited thereto.

In the present invention, the external preparation for skin hair growth inhibition may be a cosmetic composition or a pharmaceutical composition. When the external preparation for skin hair growth inhibition is formulated into medicines or cosmetics, it may contain known dermatologically acceptable excipients which act as a carrier for the active ingredient. When formulated as a medicament, the contents disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be referred to. When formulating into cosmetics, International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association , Inc., Washington, 1995, which is incorporated herein by reference in its entirety. Which are incorporated herein by reference.

Specifically, the cosmetic composition containing palmain according to the present invention can be used as cosmetically acceptable carrier, diluent, adjuvant, coloring agent, stabilizer, flavor, interfacial agent, oil, humectant, alcohol, A pH adjuster and a sunscreen agent may be further added to the composition of the present invention and the composition of the present invention may be added to the skin such as a liquid, oil, cream, ointment, stick, pack, pasta, powder, It is also available as a formulation.

For the purpose of the present invention, the cosmetic composition may preferably be manufactured from semi-solid preparations such as external ointments, lotions and the like.

In addition, the pharmaceutical composition containing palmatin according to the present invention may further comprise at least one pharmaceutically acceptable carrier, diluent, adjuvant, coloring agent, stabilizer, flavoring agent, surfactant, oil, humectant, alcohol, a pH adjusting agent and an ultraviolet ray blocking agent and may be formulated into liquid form, oil form, cream form, ointment, stick form, pack, pasta form, powder form, gel and spray form. For the purposes of the present invention, the pharmaceutical compositions may preferably be formulated as semi-solid preparations such as external ointments, lotions, and the like.

The pharmaceutical composition of the present invention may be formulated into various formulations suitable for oral administration or parenteral administration.

Non-limiting examples of such oral dosage forms include troches, lozenges, tablets, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs .

In order to formulate the pharmaceutical composition of the present invention for oral administration, a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose, or gelatin; Excipients such as dicalcium phosphate and the like; Disintegrating agents such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax may be used, and sweeteners, fragrances, syrups and the like may also be used. .

Furthermore, in the case of capsules, in addition to the above-mentioned substances, liquid carriers such as fatty oils can be further used.

Non-limiting examples of the parenteral preparation include injections, suppositories, respiratory inhalation powders, aerosol preparations for spraying, ointments, powder for application, oils, creams and the like.

In order to formulate the pharmaceutical composition of the present invention for parenteral administration, a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a lyophilized preparation, an external agent, and the like may be used. Examples of the non-aqueous solution and the suspension include propylene glycol, Polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like.

More specifically, when the pharmaceutical composition of the present invention is formulated into an injection, the composition of the present invention is mixed with water or a stabilizer or a buffer in water to prepare a solution or suspension, which is then mixed with an ampoule or a vial, And the like. When the pharmaceutical composition of the present invention is formulated into an aerosol formulation, a propellant or the like may be added together with the additive such that the water-dispersed concentrate or the wet powder is dispersed.

When the pharmaceutical composition of the present invention is formulated into an ointment, cream, or the like, it may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, a polyethylene glycol, a silicone, a bentonite, Zinc or the like as a carrier.

The route of administration and the mode of administration of the pharmaceutical composition of the present invention may be independent of each other and are not particularly limited in the method and may be arbitrarily administered and administered as long as the pharmaceutical composition can reach the desired site It is possible to follow the method. The pharmaceutical composition may be administered orally or parenterally.

The parenteral administration may be, for example, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration or subcutaneous administration, and a method of applying, spraying or inhalation the composition to a diseased site may also be used But are not limited to.

The pharmaceutical composition of the present invention may preferably be administered parenterally, and more preferably, it may be administered in a manner such that it is applied to the skin.

It is preferable that the palmain which is an ornithine decarboxylase inhibitor contained in the composition of the present invention is contained in a concentration of 0.0005% by weight to 5% by weight of the whole composition. This is because it is difficult to obtain the effect at a concentration of less than 0.0005% by weight of the component and a problem of formulation stability may occur at a concentration of more than 5% by weight.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the age, sex, weight, symptom, degree of disease, drug form, administration route and period of time of the subject, but can be appropriately selected by those skilled in the art. However, for the desired effect, the pharmaceutical composition of the present invention is preferably administered at 0.01 to 1000 mg / day. The administration can be done once a day, or divided into several times. In addition, the dose may be increased or decreased according to age, sex, weight, degree of disease, route of administration, and the like. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The present invention relates to a composition for inhibiting hair growth comprising palmatin as an active ingredient, and is excellent in the effect of inhibiting the cell differentiation or proliferation of hair follicle cells and inhibiting hair growth at a desired site of hair removal.

In addition, the composition of the present invention is advantageous in that it can be appropriately formulated to remove or reduce hairs in a local area, and has no toxicity and no side effects even when applied to a human body.

FIG. 1 is a graph showing changes in cell proliferation after treating Follicle Dermal Papilla cells with palmatin at different concentrations. FIG.
FIG. 2 is a graph showing changes in cell proliferation after treating palmatin with concentration of HT-29 cells.
FIG. 3 is a graph showing the relative expression changes of ornithine dicarboxylate after treatment of palmaine with HT-29 cells by reverse transcription PCR (RT-PCR).

Hereinafter, the constitution and effects of the present invention will be described in more detail through examples. These embodiments are only for illustrating the present invention, and the scope of the present invention is not limited by these embodiments.

Example  One: Arm Martin's Hair follicle cell  Identification of differentiation and proliferation inhibitory efficacy

In this example, the effect of palmate on the differentiation and proliferation of hair follicle cells was measured by Cell Counting Kit-8 using Follicle Dermal Papilla cell (Promo cell).

First, a uniform number of cells were plated on a 96-well plate, and then stabilized. Then, the cells were treated at different concentrations with the aid of palmatin (XI'AN JIATIAN BIOTECHNOLOGY CO., LTD. Three days after treatment, changes in cell division were measured by Cell Counting Kit-8. The degree of cell-to-cell change after 3 days of palmatin treatment is shown in Table 1 and Fig. As a positive control, α-difluoromethylornithine (DFMO), which is known as ornithine decarboxylase inhibitor, was used. The degree of cell division in the following Table 1 is shown relative to the degree of cell division of the negative control group.

sample Negative control (no treatment) Positive control (DFMO treatment) Arm Martin Sample concentration 2.5 mM 5mM 5 ug / ml 10 [mu] g / ml Relative degree of cell division 1.00 0.69 0.49 0.44 0.30

As can be seen from Table 1 and FIG. 1, Promo cell treated with palmatin showed a decrease in cell division in a concentration-dependent manner.

Example  2: Arm Martin's HT -29 cell cell division

In order to examine the effect of inhibiting the expression of ornithine decarboxylase in palmatin in this example, a colon-derived adenocarcinoma cell HT-29 cell known to have a high expression of ornithine decarboxylase was used.

The changes of cell division by palmatin treatment were measured by MTT cell proliferation assay kit based on the decrease of cell division when ornithine decarboxylase enzyme expression decreased. A uniform number of cells were plated on a 96-well plate and then treated with palmatin in a concentration-dependent manner. Cells were re-treated with palmatin while the cell culture medium was changed on the third day, and cell division changes were measured by MTT cell proliferation assay kit 4 days after the treatment with palmatin. The degree of cell-to-cell change after 4 days of palmatin treatment is shown in Table 2 and Fig. As a positive control, α-difluoromethylornithine (DFMO), which is known as ornithine decarboxylase inhibitor, was used. In Table 2, the degree of cell division was shown relative to the degree of cell division of the negative control group.

sample Negative control (no treatment) Positive control (DFMO treatment) Arm Martin Sample concentration 2.5 mM 5mM 5 ug / ml 10 [mu] g / ml Relative degree of cell division 1.00 0.69 0.48 0.32 0.24

As shown in Table 2 and FIG. 2, it can be seen that the cell division of HT-29 cells treated with palmatin decreases in a concentration-dependent manner.

Example  3: Ornithine Digital Camera  Enzyme reduction investigation

As in the cell division assay, HT-29 cells were harvested 4 days after palmatin treatment and the relative content of ornithine decarboxylase was determined after synthesis of cDNA. Changes in the ornithine dicarboxylase enzyme were determined by reverse transcription-polymerase chain reaction (RT-PCR) in order to determine the mRNA sequence of ornithine decarboxylase from human genomic DNA. The primers used at this time are shown in Table 3.

order SEQ ID NO: ODC (forward direction) 5'-tgaccacgcacatgtaaagc -3 ' One ODC (reverse direction) 5'-cattgaacgtagaggcagca -3 ' 2 GAPDH (forward direction) 5'-cgagatccctccaaaatcaa -3 ' 3 GAPDH (reverse direction) 5'-ttcacacccatgacgaacat -3 ' 4

As a result, it was confirmed that the relative mRNA level of ornithine decarboxylase in the HT-29 cells treated with palmatin was decreased in a concentration-dependent manner by palmatin treatment. The results were analyzed using the Comparative C _T (ΔΔC _T ) Experiment and the internal control using GAPDH. The results are shown in FIG.

Hereinafter, a prescription example of a cosmetic containing palmatin is shown by the production example.

Manufacturing example  1 and Comparative Example  One: Pal Martin  Manufacture of ointment for external skin containing

Skin external ointment containing palmatin (Preparation Example 1) and external skin ointment containing palmatin (Comparative Example 1) were prepared with the composition shown in Table 4 below.

Composition Production Example 1 (% by weight) Comparative Example 1 Arm Martin
Diethyl sebacate
Nonsense
Polyoxyethylene oleyl ether phosphate
Sodium benzoate
vaseline 0.5
8
5
6
Suitable amount
to 100 -
8
5
6
Suitable amount
to 100

Manufacturing example  2 and Comparative Example  2: Pal Martin  Manufacture of cream containing

A cream containing palmatin (Preparation Example 2) and a cream without palmatin (Comparative Example 2) were prepared with the composition shown in Table 5 below.

Composition Production Example 2 (% by weight) Comparative Example 2 Arm Martin
Stearic acid
ethanol
Potassium hydroxide
glycerin
Propylene glycol
antiseptic
incense
Purified water 0.2
15.0
1.0
0.7
5.0
3.0
Suitable amount
Suitable amount
to 100 -
15.0
1.0
0.7
5.0
3.0
Suitable amount
Suitable amount
to 100

Example  4: Investigation of hair removal effect

Twenty women aged 25 to 35 years who were healthy to the creams of Preparation Example 2 and Comparative Example 2 were subjected to the following hair removal effect.

The subjects were applied to the legs twice a day for 2 months with the cream of Comparative Example 2 without palmatin on the left and the cream of Preparation Example 2 containing 0.2% palmaine on the right. After 2 months, the effects of hair removal were evaluated by questionnaire and image analysis. In the questionnaire of the subjects, the change of the thickness of the hair and the growth retardation were judged to be three stages of no improvement, slight improvement, and substantial improvement compared to before use. The results are shown in Table 6.

sample No improvement Slight improvement A significant improvement Comparative Example 2 13 7 0 Production Example 2 2 10 8

As can be seen from Table 6, when the production example according to the present invention was used, it was found that the effect of hair removal due to hair thickness change and growth delay was excellent.

Example  5: Body image analysis

For image analysis of body hair, subjects were instructed to shave their legs four days before evaluation. Evaluation was carried out before and after the experiment. The results of measurement of hair growth of Production Example 2 and Comparative Example 2 by image analysis are shown in Table 7 by averaging the reduction rate with respect to hair length before the experiment.

Production Example 2 Comparative Example 2 Before experiment 1.00 1.00 after 2 weeks 0.75 (25% reduction) 0.98 (2% reduction)

As can be seen from Table 7, it can be seen that the hair growth retarding effect is significant when the production example in which palmatin is added according to the present invention is applied.

<110> LG HOUSEHOLD & HEALTH CARE LTD. <120> A body hair growth inhibition composition comprising palmatine as          an effective ingredient <130> PA130922 / KR <160> 4 <170> Kopatentin 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> forward primer for ODC <400> 1 tgaccacgca catgtaaagc 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> reverse primer for ODC <400> 2 cattgaacgt agaggcagca 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> forward primer for GAPDH <400> 3 cgagatccct ccaaaatcaa 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> reverse primer for GAPDH <400> 4 ttcacaccca tgacgaacat 20

Claims (12)

A cosmetic composition for inhibiting hair growth comprising palmatine as an active ingredient.
The cosmetic composition for hair growth inhibition according to claim 1, wherein the palmain is represented by the following formula (1).
[Chemical Formula 1]

The cosmetic composition for hair growth inhibition according to claim 1, wherein the palmain inhibits hair follicle cell differentiation or proliferation.
The cosmetic composition for inhibiting hair growth according to claim 1, wherein the palmatin inhibits the expression of ornithine decarboxylase (ODC) gene.
The cosmetic composition for hair growth inhibition according to claim 1, wherein the content of palmain is 0.0005 to 5 wt% of the total composition.
The hair growth inhibitor according to claim 1, wherein the cosmetic composition has a formulation selected from the group consisting of liquid, oil, cream, ointment, stick, pack, pasta, powder, gel and spray. Cosmetic composition.
A pharmaceutical composition for inhibiting hair growth comprising palmatine as an active ingredient.
The pharmaceutical composition according to claim 7, wherein the palmatin is represented by the following formula (1).
[Chemical Formula 1]

[Claim 7] The pharmaceutical composition according to claim 7, wherein the palmatin inhibits differentiation or proliferation of hair follicle cells.
8. The pharmaceutical composition for inhibiting hair growth according to claim 7, wherein the palmatin inhibits the expression of the ornithine decarboxylase gene.
[Claim 7] The pharmaceutical composition according to claim 7, wherein the content of palmatin is 0.0005% to 5% by weight of the total composition.
8. The method according to claim 7, wherein the pharmaceutical composition has a formulation selected from the group consisting of liquid, oil, cream, ointment, stick, pack, pasta, powder, gel and spray. A pharmaceutical composition.

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